Albumin-bound basal insulin analogues (insulin detemir and NN344): comparable time-action profiles but less variability than insulin glargine in type 2 diabetes

Diabetes Obes Metab. 2007 May;9(3):290-9. doi: 10.1111/j.1463-1326.2006.00685.x.

Abstract

Aim: This study compared the time-action profiles of the novel albumin-bound basal insulin analogue NN344 with those of insulin detemir and insulin glargine in individuals with type 2 diabetes.

Methods: Twenty-seven insulin-treated men with type 2 diabetes [body mass index 30.8 +/- 2.6 kg/m(2) (mean +/- s.d.), haemoglobin A(1c) 7.6 +/- 1.1%] were enrolled in this randomized, double-blind trial and participated in six euglycaemic glucose clamp experiments [target blood glucose (BG) 5 mmol/l] each. Participants received NN344 in three experiments at a dose of 0.8, 1.6 and 2.8 dosing units (DU) (1 DU corresponds to 6 nmol NN344) per kilogram of body weight. In the other three experiments, the participants received 0.4, 0.8 and 1.4 U/kg of either insulin detemir or insulin glargine. The insulin preparations were characterized with regards to their effects on glucose infusion rates (GIRs) (in particular duration of action and within-subject and between-subject variabilities), BG, C-peptide, free fatty acids (FFA), endogenous glucose production (EGP) and peripheral glucose uptake (PGU) over 24 h post-dose.

Results: The mean GIR profiles for all three preparations were similar in shape/flatness and showed increasing effect (area under the curve for GIR: AUC-GIR(total)) with increasing dose [low dose: 647 +/- 580, 882 +/- 634, 571 +/- 647 mg/kg (insulin detemir vs. NN344 vs. insulin glargine]; medium dose: 1203 +/- 816, 1720 +/- 1109, 1393 +/- 1203 mg/kg and high dose: 2171 +/- 1344, 3119 +/- 1549, 2952 +/- 2028 mg/kg; p = 0.48]. The duration of action increased with rising doses of all insulin preparations, without major differences between treatments. BG remained below 7 mmol/l in nearly all the experiments. Within-subject variability was lower for the albumin-bound insulin analogues, insulin detemir and NN344, than for insulin glargine (p < 0.0001). Between-subject variability did not differ between treatments, nor did the effects on BG, C-peptide, FFA, EGP or PGU.

Conclusions: In individuals with type 2 diabetes, the time-action profiles and the duration of action of the albumin-bound insulin analogues, insulin detemir and NN344, were comparable with those of insulin glargine, whereas within-subject variability in the metabolic effect was significantly lower. Therefore, insulin detemir and NN344 seem to be as well suited as insulin glargine for once-daily administration in type 2 diabetes. The better predictability may be an important characteristic of the albumin-bound analogues as insulin detemir has already been shown to improve hypoglycaemia.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Blood Glucose / analysis
  • C-Peptide / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Fatty Acids, Nonesterified / blood
  • Glucose / metabolism
  • Glucose / pharmacokinetics
  • Glucose Clamp Technique / methods
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacokinetics*
  • Insulin / administration & dosage
  • Insulin / adverse effects
  • Insulin / agonists
  • Insulin / analogs & derivatives*
  • Insulin / pharmacokinetics
  • Insulin Detemir
  • Insulin Glargine
  • Insulin, Long-Acting
  • Male
  • Middle Aged

Substances

  • Blood Glucose
  • C-Peptide
  • Fatty Acids, Nonesterified
  • Hypoglycemic Agents
  • Insulin
  • Insulin, Long-Acting
  • Lys(B29)-N(epsilon)-lithocholoyl-gamma-Glu des(b30) insulin
  • Insulin Glargine
  • Insulin Detemir
  • Glucose